Hepatocyte Growth Factor (HGF) is a heparin binding, mesenchymally-derived growth factor, that binds to a receptor encoded by the c-met protooncogene. Recent reports indicate HGF may be estrogen responsive. To characterize hormonal regulation of HGF and c-met transcripts we induced artificial menstrual cycles in spayed rhesus monkeys and collected their reproductive tracts after 14 days of estradiol (E2) treatment, after an additional 14 days of E2 plus progesterone (P) and on days 1, 2, 3, 4, 5, and 6 after P withdrawal (luteal-follicular transition; LFT). Total RNA prepared from oviduct, endometrium and cervix was analyzed for HGF mRNA by Northern blot with 32P-labeled cDNA probes, prepared from a human HGF cDNA. Total RNA was also analyzed from human M426 cells (which secrete HGF) and MCF-7 (which do not express HGF). Hybridizations revealed that the 6 kb HGF transcript was present in all regions of the reproductive tract and that HGF mRNA abundance was greatest after E2 treatment. In contrast, treatment with E2 + P decreased the abundance of the HGF mRNA. A strong positive signal was always detected in M426 fibroblasts (positive control), but no signal was ever detected in MCF-7 cells (negative control). Endometrial HGF mRNA was low at the beginning of the LFT (due to P-suppression) and increased during estrogen stimulation after P-withdrawal. This is in contrast to KGF mRNA expression, which was most abundant at the beginning of the LFT (due to P stimulation) and decreased with time after P-withdrawal. HGF receptor mRNA (met mRNA) was always detectable in the endometrium, oviduct and cervix, but did not appear to be influenced by hormonal treatment. We conclude that the HGF paracrine system may act as a mediator of E2 action in the monkey reproductive tract.